This project describes the activities of the formulation laboratory of the Pharmaceutical Resources Branch. These studies are directed toward resolving some general problems with the intravenous delivery of antitumor agents but also involve some studies to improve the solubility and stability of selected antitumor agents. Dimethylacetamide, an organic solvent, is used as a vehicle in the formulation of several antitumor agents. The compatibility of this solvent with common plasticizer-containing intravenous administration devices was evaluated using a gas chromatographic procedure to detect diethylhexylphthalate (DEHP). Extraction of substantial amounts of DEHP was not observed at the use concentrations (less than 10%). However, high concentrations of this solvent are incompatible with these devices. The plasma expander hydroxyethyl starch (hetastarch) was evaluated as a potential complexing agent for certain poorly water soluble compounds. This substance is a branched chain carbohydrate used clinically in substantial doses. Other polymers, albumin, povidone, etc. have been reported to improve drug solubility. However, only modest (less than 10 fold) increases in drug solubility have been observed to date with hetastarch. Camptothecin is a plant product with good antitumor activity in experimental model and was evaluated clinically as the sodium salt of the lactone. The clinical results were disappointing. However, this compound was reevaluated as part of the PROD activity and the pharmaceutical properties were reexamined. Modest increases in solubility were achieved by solvent-surfactant mixtures. However, a prodrug camptothecin-20-(N,N-diethyl)glycinate HCl was prepared that exhibits reasonable solubility, 5 mg/ml, and equivalent activity with the parent compound in the in vitro P388 assay.